user manual - The Rare Mitochondrial Disease Service for Adults ...

NEWCASTLE MITOCHONDRIAL NCG DIAGNOSTIC LABORATORY
Rare Mitochondrial Disorders Service for Adults and Children
Background Information to the Service
Mitochondria are ubiquitous organelles that contain their own genetic complement, the
mitochondrial genome (mtDNA). Although intimately involved in many cellular processes, their
principal task is to provide the energy necessary for normal cell functioning and maintenance.
Disruption of this energy supply can have devastating effects for the cell, organ and individual. One
important consequence of mitochondrial ubiquity is that mitochondrial disease can affect virtually
any organ and present with a plethora of symptoms and signs to a variety of specialties. These are
truly multi-system diseases with significant morbidity and mortality. Over the last two decades,
mutations in both mtDNA and nuclear DNA (nDNA) have been identified as causative in a number
of the mitochondrial clinical syndromes, although for mtDNA mutations in particular, this
relationship between genotype and phenotype is often far from straightforward. A number of
epidemiological studies have been undertaken to assess the prevalence of mitochondrial disease and
whilst rare these conditions have a major impact on both the community and individual families.
Finally, there is increasing awareness by clinicians experienced in the management of patients with
mitochondrial disease that many aspects of mitochondrial disease can be helped or prevented by
early diagnosis and subsequent care.
The Newcastle Mitochondrial Diagnostic Laboratory is an affiliated laboratory of the Northern
Regional Genetics Service, and is situated within the research laboratory space of the University’s
Mitochondrial Research Group in the Medical School. In partnership with teams at Queen Square,
Institute of Neurology (UCLH NHS Foundation Trust) and the Oxford Medical Genetics
Laboratories, Churchill Hospital (Oxford Radcliffe Hospitals NHS Trust), the Newcastle lab has
been awarded National Specialist Commissioning (NCG) funding to provide a comprehensive,
diagnostic and clinical management service for patients with mitochondrial disease in England and
Scotland – “Rare Mitochondrial Disorders Service for Adults and Children”. This multidisciplinary
service will encompass all aspects of diagnosis (muscle biopsy, histochemistry,
biochemistry and molecular genetics), utilising specialist clinical and laboratory skills available at
the three component centres, and complementing the routine analysis of common mtDNA
mutations that is available throughout the UK at many regional genetics laboratories. For many
patients with suspected mitochondrial disease, it is not possible to make a diagnosis based solely on
molecular genetic testing in blood DNA, and so for those patients where more detailed
investigations are required, a comprehensive diagnostic service is now offered which combines
clinical investigations, histochemical and histological analysis of patient muscle biopsies,
measurement of respiratory chain complex activities together with screening of both mtDNA and
nuclear-encoded mitochondrial genes.
Services offered by the Newcastle Mitochondrial NCG Laboratory
CLINICAL SERVICES
Outpatient
Consultations are available for patients and families with suspected or proven mitochondrial
disease. Clinical examination may confirm the suspicion of mitochondrial disease or suggest an
alternative diagnosis. Clear plans of investigation or patient management will be established during
the clinic appointment with close collaboration between the referring consultant and the patients
own general practitioner. Whenever possible, follow up will be at local hospitals, although some
patients with particularly rare conditions or where local services are limited may require longer term
follow up in Newcastle.
Consultations are also available for women with proven mtDNA disease or who are carriers of
pathogenic mtDNA mutations and who require advice concerning the possible transmission of the
mtDNA mutation to their children. Patients or families in which mitochondrial respiratory chain
Page 2 of 10 Date of original issue: March 2007
Revised version June 2011